The introduction of electronic cigarettes (e-cigarettes) in 2006 has created an entirely new public health dilemma. Although some public health activists believe that e-cigarettes represent a new addition to the armory of tobacco control and harm reduction, others are unsure how the widespread use of e-cigarettes will affect the prevalence of nicotine addiction and premature mortality owing to tobacco product use. The central issue in the debate is the disease risk imposed by e-cigarettes. Because e-cigarettes do not contain tobacco per se and do not burn tobacco, many of the toxic compounds produced during tobacco combustion are either eliminated or significantly reduced in abundance in e-cigarette aerosols. These devices produce little or no tar or carbon monoxide and only trace levels of metals and other toxicants abundant in combustible cigarettes. For this reason, proponents of e-cigarettes argue that many of the harmful health outcomes of combustible cigarettes, such as lung cancer, emphysema, and heart disease, are unlikely to be associated with long-term e-cigarette use. Indeed, Public Health England has declared1 and the Royal College of Physicians has agreed2 that e-cigarettes are likely to be 95% safer than conventional cigarettes. But apart from opinions, there is little direct evidence to assess the health impact of e-cigarettes.